Farnesoid X receptor modulators
The present invention provides a compound of formula (I): or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as described herein. The present invention relates generally to selective FXR agonists and to methods of making and using them.
1. A method of treating a chronic liver disease or condition in a subject, comprising administering to the subject in need thereof an effective amount of a compound of formula I:
or a pharmaceutically acceptable salt or amino acid conjugate thereof, wherein:
R 1 is hydroxyl;
R 2 is hydrogen, hydroxyl, alkyl, or halogen, wherein said alkyl is unsubstituted or substituted with one or more R a ;
R 3 is hydrogen, hydroxyl, alkyl, or halogen, wherein said alkyl is unsubstituted or substituted with one or more R b ;
R 4 is hydrogen, alkyl, alkenyl, alkynyl, or halogen, wherein said alkyl is unsubstituted or substituted with one or more R c ;
R a , R b , and R c are each independently halogen or hydroxyl;
R 5 is hydroxyl, OSO 3 H, OSO 3 − , OCOCH 3 , OPO 3 H, OPO 3 2− , or hydrogen; and
R 6 is hydroxyl, OSO 3 H, OSO 3 − , OCOCH 3 , OPO 3 H, OPO 3 2− , or hydrogen;
or taken together R 5 and R 6 with the carbon atom to which they are attached form a carbonyl,
wherein the chronic liver disease or condition is nonalcoholic steatohepatitis (NASH).
2. The method of claim 1 , wherein the compound of formula I is
or a pharmaceutically acceptable salt or amino acid conjugate thereof.
3. The method of claim 1 , wherein R 4 is alkyl.
4. The method of claim 3 , wherein R 4 is ethyl.
5. The method of claim 1 , wherein the compound of formula I is compound 100
or a pharmaceutically acceptable salt or amino acid conjugate thereof.
6. A method of treating nonalcoholic steatohepatitis (NASH) in a subject, comprising administering to the subject in need thereof an effective amount of compound 100
or a pharmaceutically acceptable salt or amino acid conjugate thereof.